FormalPara Key Summary Points

Why carry out the study?

Current European infant national immunization programs (NIPs) recommend pneumococcal conjugate vaccines (PCVs) that cover 10 to 15 serotypes and are administered in a three-dose schedule (two primary plus one booster). Recently, a PCV that offers broader serotype coverage (it protects against 20 serotypes) was licensed in a four-dose schedule (three primary plus one booster); however, the attitudes of health care providers (HCPs) and caregivers towards the PCV serotype coverage and dosing schedule in Europe remain unknown.

A total of 601 HCPs and 1,954 caregivers from four European countries (Germany, France, Spain, and Greece) completed an online survey concerning preferences for PCVs.

What was learned from the study?

Nearly all HCPs (93%) agreed that broader serotype coverage against pneumococcal disease for children is a significant unmet need, and 92% had a “sense of urgency” to vaccinate children.

Both HCPs and caregivers were supportive of an additional PCV dose and doctor visit in a situation where it would provide at least 20% more serotype coverage than what is currently available.

These results can help guide broader discussions regarding public health policy and vaccine administration in the context of important efforts to reduce the global disease burden associated with pneumococcal disease.

Introduction

Pneumococcal disease is associated with significant global morbidity and mortality [1, 2]. These infections are caused by Streptococcus pneumoniae (Spn) bacteria, of which there are more than 100 different strains or serotypes, some of which can cause serious infections (such as meningitis, bacteremia, and septicemia) as well as non-invasive disease (such as non-bacteremic pneumonia and acute otitis media) [3]. Pneumococcal disease can lead to serious complications, especially among children under the age of two, those with specific underlying conditions, and the elderly [3,4,5], with the World Health Organization (WHO) estimating that Spn bacteria are responsible for more than 300,000 deaths among children under 5 years old annually [6, 7].

The high burden of disease associated with pneumococcal infections has led to the development of pneumococcal conjugate vaccines (PCVs) for children and adults. The WHO has recommended routine immunization with the pneumococcal conjugate vaccine globally since 2007. Importantly, evidence suggests that vaccine adoption, which now includes more than 148 of the 194 WHO member states, is associated with significant reductions in severe pneumococcal disease and pneumonia [4, 5, 7, 8].

The current standard of care for childhood vaccination against pneumococcal disease in Europe covers 10–15 of the leading serotypes and is generally given in a three-dose schedule (two primary plus one booster: “2 + 1”), with the first dose given at 2 months of age, the second dose at 4 months of age, and the third dose at 11–14 months of age in most European countries [9]. Recently, a PCV that has broader serotype coverage (it covers 20 serotypes), PCV20, was licensed in a four-dose schedule (three primary plus one booster: “3 + 1”) (Fig. 1) [10,11,12,13].

Fig. 1
figure 1

This figure shows the incremental serotype coverage by available PCVs in four European countries [10,11,12,13]. PCV pneumococcal conjugate vaccine, PCV10-type  refers to serotypes that are unique to the 10-valent PCV, PCV13-type refers to serotypes that are unique to the 13-valent PCV, PCV15-type refers to serotypes that are unique to the 15-valent PCV, and PCV20-type refers to serotypes that are unique to the 20-valent PCV. *PCV10/PCV13 is recommended in Germany, but PCV13 accounts for > 90% of the uptake. All other countries recommend PCV13 in national immunization programs (NIPs). Data from France are from 2019 and for children < 2 years of age. Data from Germany are from 2017–2018 and for children < 2 years of age. Data from Greece are from 2010–2020 and for children 0–14 years of age. Data from Spain are from 2019 and for children < 2 years of age

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In Europe, the recommendation of an infant PCV program is often issued for the population by national immunization technical advisory groups (NITAGs) and/or health technology assessment (HTA) agencies. With the recent market authorization of PCV20, these decision bodies will be required to evaluate PCVs in their national immunization programs and may choose to give a non-preferential recommendation, meaning that more than one PCV may be offered, potentially under different dosing schedules. In some countries, it will be at the discretion of health care providers (HCPs) along with caregivers to choose the PCV for their practice or child, respectively.

Thus, with multiple PCV options and schedules recommended in a single European country, it will become progressively more important to understand both the HCPs and the caregivers’ current knowledge of and support for adding PCVs with different characteristics to the current childhood immunization schedule. Given the significant burden pneumococcal disease exerts in Europe and the potential far-reaching implications of implementing a PCV with more disease coverage ith an alternative dosing schedule compared with current recommendations, there remains a gap regarding HCP and caregiver understanding and perceptions of adopting this change in dosing schedule for additional serotype coverage compared withthe current standard of care.

This study seeks to gain novel insight into vaccine perceptions relating to protection against pneumococcal disease in the setting of different dosing schedules and varying degrees of protection among HCPs and caregivers in Germany, France, Spain, and Greece.

Methods

Caregivers and HCPs who met the study inclusion criteria were recruited from pre-existing internet market research panels to participate in a cross-sectional online survey. The markets of Germany, France, Spain, and Greece were chosen to represent a diverse sample of countries within the European Union in lieu of the ability to conduct the study in every country. This is a descriptive study only, and no a priori hypothesis was defined. Therefore, no formal sample size or power calculations were conducted for the study. All eligible participants that met the study inclusion criteria were included in the research and analysis. The target sample size was deemed robust and representative within funding constraints. The request to participate in research was sent via email to members of the panels who had expressed a willingness to participate in research studies. The interview request included a statement of informed consent and the set of screening questions to determine eligibility.

Caregivers and HCPs who expressed interest and were eligible to participate were directed to complete a 10-min online survey. The respondent could choose to quit the survey at any point without penalty. Upon completion of the survey, participants were compensated through their panel with a modest honorarium in line with current fair market values as determined by the study sponsor. Respondents remained blinded to the study sponsor until all questions had been answered, at which time participants were able to request details on the study sponsor, in line with local regulations.

The study (protocol # 2023-0381) was approved by Pearl Institutional Review Board (IRB) of Indianapolis, Indiana, on October 27, 2023. Informed consent was obtained from all participants prior to participating in the study. This article is based on primary data collected from human participants who consented to the study.

Study Population

Health Care Providers

Pediatricians in all countries, primary care physicians (PCPs) in France, and nurses in Greece involved in the recommendation and/or administration of vaccines to children aged 0–5 were recruited to participate in the study. PCPs were included in France and nurses in Greece due to their greater involvement in pediatric vaccination in these countries compared to other countries included in the study.

Inclusion and Exclusion Criteria

The inclusion criteria for HCPs included: (1) a practicing pediatrician (in all markets) or PCP (in France) or nurse (in Greece); (2) in practice for 3–30 years in an office-based practice; and (3) administered or recommended vaccines to patients.

Exclusion criteria included: (1) unwilling to provide informed consent or to have potential adverse events reported anonymously; (2) required consent from an employer, organization, or professional association to participate in this research, which they had not yet obtained; (3) practiced in a hospital or private clinic; (4) spent less than 75% of their professional time in direct patient care; (5) saw less than 300 pediatric patients per month as a pediatrician or less than 200 pediatric patients per month as a PCP; (6) patients aged 0–5 made up less than 20% of their patient population as a pediatrician or less than 10% of their patient population as a PCP; (7) they had not prescribed or recommended specific pneumococcal vaccines; and (8) they were affiliated with any pharmaceutical company or healthcare manufacturer, serving as a clinical investigator, conducting clinical research, or providing consulting services in any capacity.

Caregivers

Caregivers of children aged 0–5 and expectant mothers were recruited across the four European countries, as per the criteria outlined below.

Inclusion and Exclusion Criteria

The inclusion criteria for caregivers were (1) aged 18 to 55 years old; (2) residing in Germany, Spain, France, or Greece; (3) parent or legal guardian of at least one child aged 0–5 or a female currently in the third trimester of pregnancy; and (4) responsible (or shared responsibility) for making decisions concerning the health of their child. Of note, 80% of the participants were required to be aware of the existence of pneumococcal disease (e.g., pneumonia, ear infection, etc.).

Exclusion criteria for caregivers included: (1) unwilling to provide informed consent or to have potential adverse events reported anonymously; (2) consider themselves not at all supportive of vaccines (excluded because questions would not be relevant for these respondents); and (3) currently employed in the advertising/market research, public relations, pharmaceutical, or medical industry.

Study Measures

The following measures were collected from study participants and are included as supplementary material. Survey instruments were translated into local languages, and all respondents completed the survey in their local language. Whereas both HCPs and caregivers responded to the same schedule statements, each group then responded to questions tailored to their role.

Health Care Providers

HCPs provided basic demographic information, including specialty, involvement in the administration of the vaccination, regional location and setting of practice, gender, years in practice, and monthly patient volume.

HCPs were surveyed concerning the perceived importance of protection from pneumococcal diseases, the level of agreement with pneumococcal disease vaccination, the importance of attributes when considering the PCV dosing schedule, their opinion and perceptions of a 3 + 1 PCV dosing schedule, their likelihood of supporting a 3 + 1 PCV dosing schedule as a national recommendation, their opinion of parent support of a 3 + 1 PCV dosing schedule, the perceived level of burden induced by an extra dose/doctor visit for pneumococcal disease vaccination, and the sources typically relied on for childhood vaccine information.

In the HCP survey, a four-point Likert scale was used to force respondents to have positive or negative opinions. As the HCPs in this survey had all prescribed pneumococcal vaccines, they were familiar with the subject matter, and therefore a neutral option was deemed unnecessary.

Caregivers

Caregivers provided basic demographic information, including gender, type of area in which their primary residence is located (urbanicity), educational attainment, current employment status, household income, and age.

Caregivers responded to survey questions regarding the perceived seriousness of pneumococcal diseases, the importance of vaccination, their agreement on aided statements about pneumococcal diseases, their opinion on PCV schedules that include an additional dose/doctor visit, and their overall agreement with and perceptions on childhood vaccinations and sources typically relied on for childhood vaccine information. In the caregivers survey, a five-point scale was used when measuring to allow a neutral option. As such, direct comparisons between the HCP survey and caregiver survey should be viewed with caution, as the presence or absence of a midpoint option may impact the overall percentage of positive or negative responses.

Statistical Analysis

This study primarily utilized Likert scales to assess respondent agreement with and support for the questions and statements posed. Data for these questions are reported as the percentage (%) of respondents who somewhat or strongly agree with/support the question/statement. Descriptive statistics are presented for study respondents. Data for continuous variables (e.g., age) include the mean and standard deviation (SD). For categorical variables (e.g., gender and employment status), frequencies and percentages are presented.

Results

Health Care Providers

A total of 601 HCPs were recruited across the four European countries (Germany, France, Spain, and Greece). The sample distribution is summarized in Table 1. The majority of HCP respondents were pediatric providers (67%). Most (76–100%) were directly involved in the administration of vaccines to the patients in an urban (78%), office-based (75%) practice. The majority (56%) of respondents were female and had been in practice for an average of 15 years.

Table 1 Healthcare provider demographics
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Nearly all HCPs (93%) agreed that broader serotype coverage against pneumococcal disease for children is a significant unmet need, and 92% have a “sense of urgency” to vaccinate children. Across the countries surveyed, 92% of HCPs agreed that they would go out of their way to recommend a vaccine that required an additional dose if it meant more protection, and 93% would accept the time and effort needed from them and their practice to educate caregivers about the extra dose. Similarly, 94% of respondents also agreed that having a vaccination schedule that is the same for full-term and pre-term infants would be very beneficial.

HCPs were highly supportive of a new dosing schedule, assuming it garnered at least 20% more coverage than what is currently available. Across the countries surveyed, at least 91% of the HCPs would support an additional dose if (1) 20% incremental protection was provided, (2) children were protected against more medically significant strains of disease, and (3) more lives were saved or more severe disease was averted. Among HCPs, support for an additional dose or doctor visit was generally strongest among those in Spain and Greece. Findings were similar when survey results were analyzed by HCP specialty. Results are summarized in Tables 2 and 3.

Table 2 Healthcare provider survey responses—agreement with provided statements
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Table 3 Healthcare provider survey responses—extent to which respondents would support or oppose an additional dose or doctor visit
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Caregivers

A total of 1954 caregivers were recruited across the four European countries surveyed. The sample distribution is summarized in Table 4. The average age of respondents was 34 years, with the majority being married or living with a partner and reporting being a college grad or higher. Overall, the majority of respondents lived in urban areas (68%) and were female (74%).

Table 4 Caregiver demographics
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Caregivers strongly agreed on the importance of full vaccination for pneumococcal disease, even if it was associated with an additional dose and doctor visit. Doctors were highly trusted by survey respondents, with a recommendation of an extra dose deemed a strong influence on caregiver acceptance. In France and Greece, 75% of respondents were willing to pay more if it meant additional serotype coverage for their child. Caregivers were broadly supportive and willing to accept an additional dose/visit, assuming it garnered at least 20% more serotype coverage. Across the countries surveyed, at least 74% would support an additional dose if it provided significant incremental coverage, their child was protected against more medically significant strains of pneumococcal disease, or more lives were saved or more severe disease averted. Results are summarized in Tables 5 and 6.

Table 5 Caregiver survey responses—agreement with provided statements
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Table 6 Caregiver survey responses—extent to which respondents would support or oppose an additional dose or doctor visit
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Discussion

Pneumococcal disease is associated with significant morbidity, mortality, and economic burden in children [14, 15]. This burden has been reduced significantly in the era of PCVs; however, challenges remain in the development of vaccines that maximize the coverage of disease serotypes and vaccine schedules that are deemed feasible by both HCPs and caregivers.

The current study provides important and novel insight into the vaccine preferences of both HCPs and caregivers across Europe. Overall, there was unanimous agreement among HCPs and caregivers that a pneumococcal vaccine with broader serotype coverage would be desirable, and they expressed a subsequent willingness to include an extra infant dose/visit to provide added protection against pneumococcal disease. This finding is in line with similar research concerning meningitis vaccines, in which HCPs and caregivers were open to adding new vaccines to the immunization schedule, even if it required co-administration with current vaccines or the introduction of a new office visit [16].

The serotypes covered by available PCVs in the countries surveyed demonstrate that the additional incremental coverage for PCV20-unique serotypes ranges from 24 to 31% compared with PCV15 serotype coverage, ranges from 28 to 43% compared with PCV13 serotype coverage, and is 42% compared with PCV10 serotype coverage (only reported for Germany, as it is the only country to include PCV10 as an option in the national immunization programs (NIPs)) (Fig. 1) [10,11,12,13]. This additional incremental serotype coverage suggests that PCV20 could potentially protect against significantly more pneumococcal disease and, as demonstrated in this research, plays a critical role for guiding HCPs and caregivers  perceptions on the benefit of PCVs and care decisions. Importantly, European NITAGs and HTA recommending bodies may ultimately give a non-preferential recommendation for PCVs in their infant NIPs, leaving HCPs and caregivers to choose the PCV for their practice or child. Therefore, this study provides new insights into the increasing importance of HCPs and caregiver perceptions, as they may have to decide which PCV and schedule is administered to their patient/child.

The vast majority of HCPs noted a degree of urgency in developing and implementing PCVs that provide broader serotype coverage, even if this meant an additional dose for infants, and nearly all expressed a willingness to endorse a revised PCV schedule. These findings underscore the burden of pneumococcal disease on a societal scale as well as the importance of understanding the views of HCPs to help further the mission of combatting pneumococcal disease. In a study of HCP preferences for PCVs in the United States (US), the authors found that the top two attributes for a PCV are (1) the ability of the vaccine to elicit a robust immune response against vaccine serotypes and (2) the overall serotype coverage the vaccine offers against invasive pneumococcal disease [17]. PCV20 has both attributes. PCV20 elicits a robust immune response against all 20 serotypes, meeting noninferiority for at least one co–primary endpoint as measured by IgG concentrations for PCV20 under a 3 + 1 schedule [18] and meeting noninferiority for at least one primary endpoint as measured by IgG concentrations under a 2 + 1 schedule for 19 of 20 serotypes [19]. Moreover, PCV20 has incremental serotype coverage compared to lower-valent PCVs, offering the broadest coverage of any available PCV in infants to date (Fig. 1) [10,11,12,13].

Among caregivers, there was a high level of vaccine acceptance if a doctor recommended it. This is similar to findings from the Wellcome Global Monitor survey of over 140,000 individuals globally (90% of whom were in northern and southern Europe), which noted those surveyed would trust an HCP more than several other possible sources of health advice [20]. Further notable findings from our research included a broad willingness, regardless of country of origin, to undertake any extra steps to achieve effective protection of their children from pneumococcal disease. Given there was still a significant amount of caregivers who were not fully aware of pneumococcal disease, there is the potential for more education on how the disease is spread. Comprehensive waiting-room material and online disease awareness campaigns could aid with improving knowledge among caregivers. In addition, some recent evidence from a German study suggests that there is little difference in the rate of vaccination achieved with a 3 + 1 versus a 2 + 1 schedule [21], and thus characteristics of the vaccine, such as the vaccine effectiveness or serotype coverage, may take priority over caregiver preferences.

National-level recommendations for PCVs and dosing schedules may soon vary by country and/or region, thus underscoring the importance of studies, such as this one, that provide insight into HCP and caregiver knowledge levels and opinions. Similar results from our survey of HCPs were reported in another separate and recent US-based study, with 93% of the HCPs surveyed reporting a preference for PCV20 over PCV15 for children ≤ 18 years. Among those who preferred PCV20, more than 80% based their decision primarily on serotype coverage [22]. It is important to note that in the US, the Centers for Disease Control’s Advisory Committee on Immunization Practices (ACIP) currently non-preferentially recommend PCV15 or PCV20 under a 3 + 1 schedule [23], thus reinforcing the need to investigate vaccine preferences in Europe, especially with the option of PCVs under different schedules. Findings from our study are important in the context of an ongoing debate as to whether societal opinions regarding childhood vaccination should be considered when formulating disease control policies, and these survey results can add to that discussion.

Strengths and Limitations

Strengths of the current study include the surveying of respondents across several European countries, the inclusion of both HCPs and caregivers, and the relevance and potential implications of the study question for societal public health. Further, the results of this survey broadly aligned with existing studies that have examined similar topics, suggesting that the questions were appropriate and the data garnered were meaningful.

Despite these strengths, it is important to acknowledge that the method and the nature of self-report surveys rely on the willingness of respondents to be involved in a research panel, which invites the possibility of selection bias. Further, as with any research that relies on convenience sampling, it is possible that certain types of participants may be over-represented and that the results may not generalize to the entire population. Finally, surveys regarding hypothetical scenarios, such as a willingness to pay for or schedule an additional medical visit, are not 100% reliable indicators of future behavior. Further, different Likert scales were used for HCPs and caregivers surveyed in the study, and thus caution is warranted in drawing comparisons.

Conclusions

The current study provides critical insight into pneumococcal vaccine opinions and perceptions in Europe. HCPs and caregivers were virtually unanimous in their support for a PCV with broader serotype coverage and expressed a subsequent willingness to include an extra infant dose/visit. These results can help guide broader discussions regarding public health policy and vaccine administration in the context of important efforts to reduce the global disease burden associated with pneumococcal disease. There is ongoing debate as to whether societal preferences for childhood vaccination should be considered when formulating national immunization policies, and these survey results can add to that discussion.